ClinicalTrials.gov record NCT04099797
C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)
Phase I Study of Autologous T Lymphocytes Expressing GD2-specific Chimeric Antigen and Constitutively Active IL-7 Receptors for the Treatment of Patients With GD2-expressing Brain Tumors (GAIL-B)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Phase 1 study testing an investigational CAR T cell product (GD2-C7R) in children and young adults with GD2-expressing high-grade or embryonal brain tumors. Patients give blood to make their own modified T cells, receive short chemotherapy to make room for the cells, then get an IV infusion followed by injections into the brain fluid through an Ommaya reservoir or programmable VP shunt. The study seeks the largest safe intracerebroventricular dose and will monitor how long the cells are detectable and how tumors respond. Long-term follow-up for gene-transfer safety is planned.
What it is studying. The study is testing the safety and appropriate dose of autologous (patient-derived) T cells engineered with a GD2-targeting chimeric antigen receptor plus a C7R gene meant to support cell survival. It tests giving a standard IV infusion first, then one or more injections directly into the brain's cerebrospinal fluid using an Ommaya reservoir or programmable VP shunt. The study will measure short-term toxicities, how long the modified T cells can be detected in blood and spinal fluid, and tumor response on MRI.
What the researchers hope to learn. Determine the largest safe intracerebroventricular dose of GD2-C7R CAR T cells; measure dose-limiting toxicities within the early safety period; assess how long the infused cells persist in blood and cerebrospinal fluid; evaluate tumor response by MRI.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare high-grade glioma that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive diffuse intrinsic pontine glioma that expresses GD2. Because there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that help the body fight infection. This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat cancer patients. They have shown promise but have not been strong enough to cure most patients. Researchers have found from previous research that they can put a new antibody gene into T cells that will make them recognize cancer cells and kill them. GD2 is a protein found on several different cancers. Researchers testing brain cancer cells found that many of these cancers also have GD2 on their surface. In a study for neuroblastoma in children, a gene called a chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2. This gene was put into the patients own T cells and given back to 11 patients. The cells did grow for a while but started to disappear from the blood after 2 weeks. The researchers think that if T cells are able to last longer they may have a better chance of killing tumor cells. In this study, a new gene will be added to the GD2 T cells that can potentially cause the cells to live longer. T cells need substances called cytokines to survive. The gene C7R has been added that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. In other studies using T cells researchers found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively. After treating 11 patients, the largest safe dose of GD2-CAR T cells given in the vein (IV) was determined. We are now combining an IV infusion with an infusion directly into the brain through the Ommaya reservoir or programmable VP shunt. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way. Patients will now be assigned to Cohort 1 and 2 based on their tumor type. The GD2.C7R T cells are an investigational product not approved by the FDA. The purpose of this study is to combine infusions into the vein in the first treatment cycle with infusions directly into the cerebrospinal fluid (CSF) in the brain (intracerebroventricularly) through the ommaya reservoir or programmable VP shunt for infusions cycles 2-24. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way, and additionally to evaluate how long they can be detected in the blood and CSF and what affect they have on brain cancer.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Genetic
- C7R-GD2.CART cells (IV and ICV infusion)
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Procurement Inclusion Criteria:
- Cohort 1:
- Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence.
- OR
- Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG/HGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available.
- OR
- Recurrent, refractory, or progressive high-grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma "CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas or glioneuronal tumors.
- Cohort 2:
- Recurrent, refractory, or progressive pontine HGG with confirmed GD2-expression or H3K27-altered DMG
- Tumors less than 5 cm in maximum dimension at enrollment
- Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
- Tumors with >25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with pre-irradiation MRI.
- Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
- Measurable disease on at least 2 dimensions on MRI
- Age 12 months to 25 years
- Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2)
- Procurement
Exclusion criteria
- Patients who are pregnant or breast feeding
- Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.
- Treatment Inclusion Criteria
- Cohort 1:
- Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence.
- OR
- Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG/HGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available.
- OR
- Recurrent, refractory, or progressive high -grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma, CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas, or glioneuronal tumors.
- Cohort 2:
- Recurrent, refractory, or progressive pontine H3K27-altered for DMG or HGG with confirmed GD2-expression.
- Tumors less than 5 cm in maximum dimension at enrollment
- Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
- Tumors with >25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared pre-irradiation MRI
- Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
- Measurable disease on at least 2 dimensions on MRI
- Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed. Central line/PICC may be omitted for cycles that do not include lymphodepletion
- Age 12 months to 25 years
- Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2)
- Patients must have completed standard of care radiation therapy at least 4 weeks prior to administration of investigational agent. If bevacizumab was administered for management of radiation necrosis, therapy must be completed at least 4 weeks prior to administration of investigational agent.
- Stable neurologic exam for 7 days prior to enrollment
- Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg/kg/day over the past 7 days prior to infusion of investigational therapy)
- Organ function:
- ANC > 1000 cells/ul
- Platelet count > 100,000 cells/ul
- Total bilirubin < 1.5x ULN
- ALT and AST < 5x ULN
- Serum creatinine or kidney within 2x ULN for age
- Treatment Exclusion Criteria
- Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
- Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion
- Patients receiving any concurrent anti-cancer therapy (treatment must occur at least three half-lives following prior anti-cancer therapy)
- Patients who are pregnant or breast feeding
- Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
To prepare the brain cancer specific GD2-C7R T cells, research staff will take some blood from the patient. The researchers will grow the GD2.C7R T cells by infecting the T cells with a retroviral vector (a special virus that can carry a new gene into cells) containing one gene that can recognize and kill brain cancer cells GD2.CAR and the new gene called C7R that will help these cells survive longer. After the new genes have been put into the T cells, the cells will be tested to make sure that they kill GD2-positive brain cancer cells. All patients on this study are required to have an Ommaya catheter in place prior to treatment as a precaution and for infusion of the T cells. This is a special catheter that leads to the tumor, the cavity left in the brain after surgical removal of the tumor, or into the fluid-filled space in the brain. Catheter placement is done by a surgeon and requires anesthesia and is not part of this study. Patients who had a programmable VP shunt placed for other clinical reasons are also eligible. Because the researchers are growing the cells in the laboratory, blood to test for infectious viruses such as hepatitis and HIV (the virus that causes AIDS) will be collected, and patients will complete a blood donor questionnaire. The cells generated will be frozen and stored to give back to the patient. Because patients will have received cells with a new gene in them patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer. All patients will be given the IV treatment and the dose is adjusted based on body weight and height. Patients in Cohort 1 and Cohort 2 will then be assigned a dose of GD2-C7R T cells to be given directly into the brain (intracerebroventricularly ICV) via Ommaya or programmable VP shunt. . In this study, patients will receive the GD2-C7R cells and also receive cyclophosphamide and fludarabine (or clofarabine in cases of fludarabine shortage). These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them. Cyclophosphamide and fludarabine (or clofarabine) will be given intravenously (through an IV needle inserted in a vein or a central line) for 2 days and then fludarabine (or clofarabine) alone on the third day. Before patients receive IV T cell infusion, patients may be given a dose of Benadryl and Tylenol. Patients will receive GD2-C7R cells through an IV. The infusion will take between 1 and 5 minutes. Patients will be monitored for 5 days. Treatment for 2nd and subsequent treatment cycles: Cohort 1: Patients will be given an injection of GD2-C7R T cells intracerebroventricularly (ICV) through the ommaya reservoir or programmable VP shunt at the assigned dose. Patients will then be monitored in the hospital for at least 5 days. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital. The patient will be readmitted to the hospital if the patient develops a fever or other concerning side effects. Cohort 2: On Day 0, patients will receive an injection of GD2-C7R cells intracebroventricularly through the Ommaya reservoir or programmable VP shunt at the assigned dose. The infusion will take between 1 and 5 minutes. Patients will then be monitored in the hospital for at least 5 days. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital. Patients will be readmitted to the hospital if the patient develops a fever or other concerning side effects. Patients will be monitored at least 5 days after each infusion and until resolution of CRS and neurotoxicity. Starting with the 3rd treatment cycle the minimum inpatient monitoring can be decreased to 3 days if the prior treatment cycle was tolerated. If the patient develops fevers or other concerning symptoms after discharge from the hospital within the safety observation period of 4 weeks, the patient will be readmitted to the hospital for close monitoring for at least one night. All patients will have follow-up visits at weeks 1, 2, 3, 4, 6, and 8, then at months 3, 6, 9, and 12, and then twice a year for the next 4 years and annually for the next 10 years for a total of 15 years, with additional neurological evaluations in the first 4 to 6 weeks. The patient will also have scheduled disease evaluations after the T-cell injection between weeks 4 to 6 and then as clinically needed. After disease re-evaluation, the patient may be eligible to receive up to 24 additional cycles of T cells if the following criteria are met: (1) The disease has not gotten worse and/or it seems the patient may benefit in the future from an additional dose. (2) The patient has not had a severe side effect caused by the infusion of GD2-C7R T cells. The dose will be at the same dose level as the first ICV infusion and separated by at least 4 weeks such that the researchers can make sure there are no severe side effects between infusions. If the patient receives an additional dose of GD2-C7R T-cells, then the patient will need to stay in Houston for up to 4 weeks after the infusion as well to monitor for side effects. Starting with the 4th cycle the minimum time in Houston can further be reduced to 1 week if the previous cycles were well tolerated. Medical tests before treatment-- Before being treated, the patient will receive a series of standard medical tests:
- Physical exam
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by routine MRI (Magnetic Resonance Imaging)
Medical tests during and after treatment-- The patient will receive standard medical tests when they are getting the infusions and afterwards:
- Physical exams
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by MRI imaging studies and spinal fluid analysis 4- 6 weeks after the infusion and repeat MRI imaging at 3 months.
Spinal Fluid Tests: Spinal fluid will be drawn from the patient's existing Ommaya reservoir or VP shunt (if clinically feasible) at the time of ICV infusion and at week 1, and 4 and possibly other timepoints if helpful for clinical care. This procedure can be done at the bedside under local anesthesia and 1-10 ml of spinal fluid will be removed. Additional spinal fluid may be removed if the pressure inside the brain is elevated. Additionally, spinal fluid may be removed for clinical reasons, for example testing for a possible infection. Spinal fluid may be used for research purposes, for example to better understand how the infused T cells work, and in future research studies. To learn more about the way the GD2-C7R T cells are working and how long they last in the body, an extra amount of blood will be obtained on the day that chemotherapy starts, the day of the T-cell infusion(s) and at the end of the T-cell infusion(s), 1, 2, 4, 6 and 8 weeks after the T-cell infusion(s) and every 3 months for the 1st year, every 6 months for the next 4 years and annually for the next 10 years. The amount of blood taken will be based on weight with up to a maximum of 60 mL (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon) per 1 kg of body weight on any one day. This volume is considered safe, but may be decreased if the patient is anemic (has a low red blood cell count). During the time points listed above, if the GD2-C7R T cells are found in the patient blood at a certain amount, an extra 5 mL (about 1 teaspoon) of blood may need to be collected for additional testing. If the patient has a procedure where tumor samples are obtained, like a blood is collected or tumor biopsy, a sample will be requested to be used for research purposes. The patient will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as appropriate.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
If enrolled, you give blood so your own T cells can be grown and modified in the lab, and you must have an Ommaya reservoir or programmable VP shunt (placement surgery is done separately if needed). You receive short courses of lymphodepletion chemotherapy by IV, then an IV infusion of the modified GD2‑C7R CAR T cells (cycle 1) and later injections into the cerebrospinal fluid (intracerebroventricularly) through the Ommaya or VP shunt for cycles 2–24; each infusion requires inpatient monitoring for at least 5 days and until cytokine release syndrome (CRS) and neurological side effects have resolved, and from the third treatment cycle the minimum stay can be reduced to 3 days if the previous cycle was tolerated. Spinal fluid samples (1–10 mL) will be taken from the reservoir/shunt at several timepoints and blood samples are collected frequently, with long‑term follow‑up for up to 15 years to monitor effects of the gene transfer; tumor biopsy or sample donation may be requested if clinically obtained. You will receive standard supportive care for side effects and may be readmitted for fever or other concerning symptoms during the safety observation periods.
How the study is structured. Phase 1, interventional, non-randomized, open-label study with two parallel cohorts by tumor type. Blood is collected to manufacture personalized GD2-C7R CAR T cells. Participants receive lymphodepleting chemotherapy, an IV T-cell infusion in cycle 1, and intracerebroventricular (ICV) T-cell infusions for later cycles via an Ommaya reservoir or programmable VP shunt. ICV dose levels are tested to find the largest safe dose. Patients are monitored in hospital after each infusion and followed long term (up to 15 years) for safety and cell persistence.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry lists this study under Diffuse Intrinsic Pontine Glioma; High Grade Glioma; Embryonal Tumor; Ependymal Tumor. Does it apply to my diagnosis?
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Gaucher disease
Important dates
- Study start
- Feb 3, 2020
- Primary completion
- February 2027 (estimated)
- Study completion
- February 2041 (estimated)
- Target enrollment
- 56 participants (estimated)
- Last updated on registry
- Aug 3, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Baylor College of Medicine
- Principal investigator
- Jasia Mahdi, MD, Assistant Professor
Baylor College of Medicine - Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- The Faris Foundation
- ChadTough Defeat DIPG Foundation
- Violet Foundation for Pediatric Brain Cancer
- DIPG DMG Research Funding Alliance
- Cancer Prevention Research Institute of Texas
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Jasia Mahdi, MD 📞 832-822-1750 ✉ Jasia.Mahdi@bcm.edu
- David Allen 📞 832-824-4391 ✉ dlallen@bcm.edu
Participating sites (1)
- Texas Children's HospitalRecruiting
Houston, Texas, 77030 · United States
- Bilal Omer, MD · 832-824-6855 · bomer@bcm.edu
- David Allen · 832-824-4391 · dlallen@bcm.edu
Terms used on this page · explanations by MedicalUpdates.ai
- Cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- standard treatment
- Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
- chimeric antigen receptor
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- investigational product
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Histologically confirmed
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- MRI
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- Karnofsky
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- ANC
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- ICV
- Given directly into the fluid-filled spaces (ventricles) inside the brain, usually through an implanted catheter or reservoir.
- CRS
- A reaction in which the immune system releases a large amount of signalling proteins at once, causing fever and sometimes low blood pressure or breathing problems. It can occur after some immune therapies, such as CAR-T cells or bispecific antibodies.
- prior treatment
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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